Northwestern University Feinberg School of Medicine associate professor of medicine Alan L Buchman MD is conducting a study of patients receiving total parenteral nutrition (TPN) in order to confirm an earlier study showing that supplementing the B vitamin choline prevents the development of fatty liver. Fatty liver, which often occurs with alcoholism and obesity, can lead to cirrhosis or liver failure. Previous research conducted on choline by Dr Buchman led to the U.S. Food and Drug Administration's approval of nutritional label content claims for choline last year. In the current FDA-funded study, U.S. and U.K. patients receiving TPN who have had part of their intestines removed will be given choline or a placebo in their intravenous solutions and monitored for liver damage. TPN solutions have not contained choline because of the belief that humans manufacture their own choline and that breaks it down very slowly. Dr Buchman explained, "They do metabolize it very slowly, but it doesn’t mean they don’t metabolize it. Without a source, regardless of how slowly choline is metabolized, eventually the body’s supply will be depleted... When we gave choline intravenously, we were able to get the blood levels of choline to normal and all the fat in the liver went away."

Although choline exists in a variety of foods, its principle sources, organ meats and fatty foods, may be shunned by many individuals. Oral choline supplements can create a fishy body odor in some individuals, however the intravenous route of administration eliminates that problem.

Dr Buchman commented on choline's additional benefits, "Although we’ve known about choline for a while, we’re just now discovering its importance to verbal and visual memory, nerve conduction, and communication between the cells of the body."

April 26, 2002

Calcium supplements offer postmenopausal women heart protection

The April 1 2002 issue of the American Journal of Medicine published the results of a controlled trial which demonstrated that calcium citrate supplements improve lipid concentrations in postmenopausal women. Two hundred twenty three women who were not being treated for hyperlipidemia or osteoporosis were randomized to receive one gram calcium in the form of calcium citrate, or a placebo for one year. Fasting high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) and triglyceride levels were measured at the study's onset and at two months, six months and one year.

At the trial's conclusion, the women who received calcium had higher HDL levels, greater HDL to LDL ratios, and a slight decline in LDL cholesterol levels compared to the placebo group.

Research team leader Dr Ian R Reid, Professor of the Department of Medicine at the University of Auckland in New Zealand, summarized, "This study showed that 1 gram of calcium (as the citrate) taken daily lowers the damaging component of blood cholesterol (LDL or low-density lipoprotein), and increases the protective cholesterol (HDL or high-density lipoprotein). As a result, calcium citrate may reduce the incidence of heart attacks and angina in postmenopausal women. Based on our data, one could predict that calcium citrate supplements may help otherwise healthy postmenopausal women reduce cholesterol, improve heart health and possibly even reduce the rate of cardiovascular related events by 20 to 30 percent. These data provide reason to encourage the more widespread use of calcium supplementation in postmenopausal women... Our results indicate that the benefits of calcium supplementation go beyond osteoporosis.”

The authors conclude that calcium leads to positive changes in lipids and write, "This suggests that a reappraisal of the indications for calcium supplementation is necessary, and that its cost effectiveness may have been underestimated." (Reid, et al, American Journal of Medicine, volume 112, issue 5, pp 343-347.)

April 24, 2002

Moderate caloric restriction reduces polyp formation in mice

A study conducted at the National Cancer Institute and reported at the Experimental Biology 2002 meeting held in New Orleans this month demonstrated that mice receiving moderately calorie restricted diets developed 60 percent fewer precancerous intestinal polyps than mice who were allowed to eat as much as they wanted. The research team, headed by Dr Steve Hursting, measured the food intake of a strain of mice at high risk of gastrointestinal cancers who were allowed to gain weight on an ad lib diet, and provided a separate group with a diet consisting of 60% this calorie intake yet containing a sufficient amount of nutrients to satisfy the animals' requirements. The calorie restricted diet reduced the number of precancerous polyps by 60%, thereby lowering the animals' risk of colon cancer.

In another experiment, one group of mice was fed a high fat diet, another received a diet providing a fruit and vegetable extract and utilizing olive oil as its source of fat, and a third group received a standard laboratory diet. None of the groups' calorie intake was restricted. The mice receiving the diet containing olive oil, fruits and vegetables developed one third fewer polyps than the group on the control diet, while mice on the high fat diet experienced a slightly higher number of polyps than the controls. Moderate exercise was found to lower the number of polyps that formed by an insignificant amount.

The report was presented at the Experimental Biology 2002 meeting on April 23 by research team member and NCI Cancer Prevention Fellow in the Nutritional Epidemiology Branch, Dr Volker Mai. Dr Mai stated that the researchers are planning to study the effects of various combinations of calorie and fat intake as well as exercise in order to determine which combinations have sufficient potential for clinical studies.

April 22, 2002

Ginkgo improves cognitive ability in MS

Dr Jody Corey-Bloom of the University of California San Diego School of Medicine reported the latest findings of a pilot study on ginkgo and multiple sclerosis at the annual meeting of the American Academy of Neurology held in Denver from April 13 through April 20. In a double-blind placebo-controlled modified crossover study of twenty-three patients with a mild form of the disease, one group was randomized to receive a placebo for three months before receiving 240 milligrams ginkgo per day for an additional three months, while a second group of subjects was randomized to receive ginkgo for six months. The groups were similar in regard to gender, age and education. Both groups received several tests of cognitive function including the Paced Auditory Serial Addition Test, Delis-Kaplan Executive Measures Scale and California Verbal Learning Test at the beginning of the study, and after three and six months. Well-being was assessed by the participants' completion of several subjective assessments, including the Beck Depression Index, the Modified Fatigue Impact Scale and the Multiple Sclerosis Quality of Life Index, at the study's baseline and at the three and six month marks.

In the group receiving ginkgo, significant improvement on one of the cognitive function tests and on one of the quality of life assessments occurred. The placebo group significantly worsened in one of the test categories. A correlation emerged between the status patients' perceived cognitive abilities and the presence of fatigue. No adverse events were reported.

As few drug therapies have been demonstrated to slow the loss of cognitive function, future studies with larger populations may prove ginkgo to be a valuable intervention in multiple sclerosis.

April 19, 2002

Longest multiple sclerosis trial in history shows good results for drug

The American Academy of Neurology's annual meeting in Denver was the site of the announcement that an eight year study of the drug glatiramer acetate, or Copaxone R, on multiple sclerosis patients has shown great success. In a double blind trial beginning in 1991 two hundred fifty-one patients with relapsing-remitting multiple sclerosis were randomized to receive glatiramer acetate or a placebo . After thirty months, the placebo group was also given the drug. One hundred forty-two patients continued with the study. Participants were evaluated for disability status every six months.

Disease symptoms in 65% of the seventy-two participants who received the drug for eight years remained unchanged or improved. In the group that initially received the placebo, half were improved or their condition remained unchanged. The majority of participants had multiple sclerosis for an average of fifteen years at which time the disease usually necessitates a walking aide. Yet most of those receiving the drug for eight years could walk without assistance.

Study author Dr. Kenneth P. Johnson, Director of the Maryland Center for MS University of Maryland, Baltimore summarized the results, "Three findings in this eight year Copaxone trial are that (one) the patients have a very low relapse rate: they went from one and a half attacks per year down to one every five years or less. Secondly that 65% of the patients always on the drug are the same or better than they were eight years ago, and finally, the drug, even though it's a daily injection, is well tolerated, it's safe, and it's something that patients are willing and anxious to continue with because they think it's helping."

April 17, 2002

Folic acid supplements help ensure women's needs

Readers of Life Extension's "What's Hot" feature may recall an item published on March 21, 2001 entitled, "Food fortification with folic acid not enough." The article discussed the attempt to determine if the current average intake of folic acid, which has been boosted over the last few years with the advent of flour fortification, is sufficient to lower homocysteine. The authors concluded that only a small number of individuals are receiving enough folic acid to lower homocysteine to optimal levels.

The latest study, conducted at Purdue University in West Lafayette, Indiana, sought to determine the benefits of the greater bioavailability of synthetic folic acid in supplements and in fortified food in adult women. Participants in two 1997 health screening events ages 18 to 89 completed food frequency questionnaires and folic acid intake was calculated. Women ages 18 to 46 consumed more bread group servings than those age 55 to 89, thereby benefiting more from flour fortification. While most women met the new average requirement, sixty-one percent of women of childbearing age were found to have intakes of synthetic folic acid lower than the 400 microgram per day recommended level. Those who used supplements were the only ones in this age bracket to consume this amount of synthetic folic acid.

The researchers concluded that folic acid at its current level should improve the intakes of many women, particularly when accompanied by folic acid supplements. In women with limited resources these benefits may not be seen, and under existing standards, a large number of women of child-bearing age will not meet the current recommendations for neural-tube defect prevention.

The study was published in the October 2001 issue of the journal Nutrition.

April 15, 2002

Arginine completely reverses arteriolar thrombosis in animal model

A study published in the April 1 2002 issue of the journal Arteriosclerosis, Thrombosis, and Vascular Biology sought to determine the effect of high cholesterol on thromboembolism, which is the blockage of a blood vessel by a portion of a blood clot. The second aim of the study was to determine whether changes in nitric oxide production are involved in the effect of high cholesterol on thromboembolism.

High cholesterol diets were given to eight rabbits for two weeks to induce high serum cholesterol while seven rabbits were given a similar but cholesterol free diet. Following this period, the animals were anesthetized and thromboembolic reactions were induced by injury to the arterioles and venules, which are the smaller vessels that branch from the arteries and veins. Two similarly fed groups of animals received superfusions of an arginine-containing solutions.

In each of the four groups, the amount and duration of embolus production were much greater in arterioles than venules. High cholesterol caused a significant increase in the duration and height of embolisms in arterioles, and the presence of L-arginine completely reversed the prolongation of embolization duration in the high cholesterol group. These effects were not seen in venules. The increase in mean arterial blood pressure seen in the rabbits receiving high cholesterol diets was reversed by L-arginine.

The Dutch researchers write that the effect of high cholesterol on increased embolization in arterioles can be completely reversed by L-arginine, due to its function as a precursor of endogenous nitric oxide, which reduces reactive oxygen species. The absence of an effect of L-arginine on thromboembolism in the venules could mean that the synthesis of nitric oxide is already at its maximum level in these vessels.

April 12, 2002

Large study shows fish oil supplements reduce sudden cardiac death

The outcome of the GISSI-Prevenzione trial, conducted by researchers in Italy on 11,323 patients, and published online in Circulation: Journal of the American Heart Association, showed that one gram daily of fish oil derived fatty acid supplement taken for three months reduced the risk of sudden cardiac death from arrhythmia by one half compared to those who received a placebo.

Lead author Roberto Marchioli MD, of Consorzio Mario Negri Sud in Santa Maria Imbaro, Italy, stated, "That was a surprise. The risk of death, and sudden death, is higher in the first months after a heart attack. It is exactly in this period that the effect on sudden death was noted.”

In an attempt to determine the time course of the benefits of omega-3 polyunsaturated fatty acid supplements, recent heart attack survivors were randomized to receive the fatty acids, vitamin E supplements, both supplements or a placebo. Total mortality was significantly lowered in the group receiving the fatty acids at three months, and the risk of sudden death was significantly lowered at four months. These trends continued, to reveal a similar reduction in the risk of heart related deaths at six and eight months. The risk reductions were not associated with changes in cholesterol levels or by decreases in blood coagulation.

In an accompanying editorial, Alexander Leaf MD, of Harvard Medical School, discussed the ability of fatty acids to regulate the electrical activity of heart muscle cells, and stated that the findings of this study support the theory that an imbalance of omega-3 and omega-6 fatty acids promote arrhythmias. He commented, "This study is important because there is no really effective therapy for arrhythmias."

The ninety-third annual meeting of the American Association for cancer Research was the site of a presentation demonstrating that green tea drinkers in China have approximately half the rate of cancer of the esophagus and stomach as those who drink little tea. Researchers at the Keck School of Medicine at the University of Southern California analyzed data collected from 18,244 Chinese men ages forty-five to sixty four during which 42 men were diagnosed with esophageal cancer and 190 with stomach cancer. The men were followed from 1986 to the present. Participants diagnosed with cancer were compared to 772 men who did not have cancer. Green tea polyphenols, the ingredients believed to be responsible for the benefits conferred by drinking tea and which include epigallocatechin and epicatechin and polyphenol breakdown products were measured in the urine of both groups.

The researchers found that epigallocatechin's presence in the urine was associated with a lowered incidence of esophageal and gastric cancer, after adjustment for other factors such as smoking and alcohol drinking. It is believed that the powerful antioxidant properties of green tea polyphenols are responsible for their anticancer effect, by protecting proteins DNA from oxidative damage.

Research team member and professor of preventive medicine at Keck School of Medicine Mimi C. Yu, PhD, summarized, "This study provides direct evidence that tea polyphenols may act as chemopreventive agents against gastric and esophageal cancer development."

April 08, 2002

Vitamins C and E protect heart transplant patients

To confirm whether the administration of antioxidant vitamins could slow the progression of arteriosclerosis due to increased oxidative stress observed in 70% of heart transplant recipients, researchers at the Brigham and Women's Hospital in Boston and the Linus Pauling Institute in Corvallis, Oregon conducted a double-blind study on forty transplant patients, who received antioxidant vitamins or a placebo for one year. The patients, who were enrolled in the study within two years following their transplant surgeries, were randomly given 400 international units vitamin E and 500 milligrams vitamin C or a placebo twice per day. Plasma concentrations of the vitamins were assessed at the study's onset and at one year. The patients received coronary angiography, intravenous ultrasound and testing of coronary endothelial vasomotor function before and at the end of the study period. Both groups received the drug pravastatin.

The intimal index, a measure of inner arterial wall thickness, increased by 0.8% in the group taking vitamin C and E compared to an 8% increase in the group who received the placebo. Areas of atherosclerotic plaque increased in the group receiving the placebo while diminishing in the group receiving vitamins. The amount of change observed in the maximum thickness of the intima was significantly less in the group receiving C and E.

The researchers note that the benefits seen in this study occurred mainly by the inhibition of plaque rather than by vessel shrinkage, and that this inhibitory effect was greater than that previously observed to have been conferred by statin drugs. They suggest that antioxidant therapy with vitamins C and E may be helpful in kidney, lung and liver transplants, in which the obliteration of tubular or vascular structures can become problematic.

Researchers at the University of Colorado in Boulder believe that oxidative stress may be involved in the decline in resting metabolism observed in older individuals, and that vitamin C, by combating oxidative stress, may help reverse the trend. Assistant Research Professor Pamela Parker Jones of the kinesiology and applied physiology department of UC Boulder is conducting a study of individuals over the age of sixty in order to find out.

Earlier studies led by Dr Jones have indicated that older individuals burn fewer calories at rest than younger adults. A study published in the September 2001 issue of The Journal of Clinical Endocrinology & Metabolism showed that this lower metabolic rate is due to a diminished ability of the nervous system to support resting metabolism, which may be related to the interference of increased oxidative stress that occurs with aging . Administering the antioxidant vitamin C might remove that stress and increase resting metabolism.

Dr Jones summarized, “It is possible that the removal of oxidative stress using vitamin C could lead to a significant increase in resting metabolism in these older adults,” said Jones. “This has important implications for reducing age-associated weight gain.”

Preliminary experiments involving intravenous infusion of the vitamin to older individuals has shown that vitamin C provides an increase in resting metabolic rate of 100 calories per day.

Department of Kinesiology and applied physiology research associate Christopher Bell explained, "We can combat the effects of oxygen free radicals by giving older adults substances known as antioxidants. The body produces an abundance of antioxidants when we are young, but as we age, the production goes down. This increases the importance of healthy eating for older adults because foods such as fruit and vegetables are rich in antioxidants.”

April 01, 2002

St John's Wort extract fights cancer

Researchers from the University of Freiburg, in Freiburg, Germany have discovered that hyperforin, a natural antibiotic found in the herb St John's Wort, inhibits tumor cell growth. The research was published in the February 14 2 02 issue of the journal Oncogenehttp://www.naturesj.com/onc/index.htm, one of the top five cancer research journals in the world. The scientists found that the compound induced apoptosis, or programmed cell death in sixteen human and rat tumor cell lines. Although many of the cell lines were resistant to such common chemotherapeutic drugs as camptothecin, paclitaxel and vincristine, hyperforin arrested tumor growth in all but one line. In vivo, hyperforin was able to inhibit the growth of breast cancer cells injected into rats as well as paclitaxel, however, hyperforin did not produce any signs of toxicity, as is commonly elicited by chemotherapeutic drugs.

The researchers, led by C M Schempp of the University of Freiburg's Department of Dematology, believe that their investigations demonstrate that hyperforin's mechanism of action is that of activating a mitochondrial-mediated apoptosis pathway. Mitochondria are the cell's energy-producing organelles. Mitochondria of cells treated with hyperforin were observed to rapidly lose membrane potential as well as release cytochrome c, which is necessary for apoptosis. The authors conclude, "Owing to the combination of significant antitumour activity, low toxicity in vivo and natural abundance of the compound, hyperforin holds the promise of being an interesting novel antineoplastic agent that deserves further laboratory and in vivo exploration."

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